This application proposes to develop a bioartificial liver (BAL) to be used as a bridging device to liver transplantation or for spontaneous recovery for patients with acute liver failure. The problems with the currently developed BAL are that the liver cells lose important synthetic and biotransformation functions. Preliminary work from the laboratory suggests that cell/cell and cell/matrix interactions are important for hepatocyte differentiation and function. The hypothesis of the grant is that by understanding and manipulating adhesion receptors involved in cell/matrix and cell/cell interactions that hepatocyte differentiation and biotransformation can be improved, and therefore improve the efficacy of a BAL. The Specific Aims are: 1. To demonstrate that adhesion receptor interactions between rat or porcine hepatocytes and the culture substratum or other liver cells regulate biotransformation functions; 2. Drug induction of P450 is matrix dependent and will enhance the biotransformation capacity of the BAL; 3. To demonstrate that an optimized BAL consisting of matrix entrapped hepatocyte spheroids pretreated with a combination of P450 inducers will provide superior therapeutic efficacy in a canine liver failure model.